Effect of phenobarbital on the level of translatable rat liver epoxide hydrolase mRNA.

Liver poly(A)+RNA isolated from untreated and phenobarbital-treated rats has been translated in the rabbit reticulocyte cell-fre system in order to determine the level of translationally active epoxide hydrolase (EC 3.3.2.3) mRNA. The in vitro translation systems were immunoprecipitated with rabbit IgG prepared against purified epoxide hydrolase, and the amount of epoxide hydrolase synthesized by the lysate programmed with control and phenobarbital poly(A)+RNA was quantitated. The level of translatable epoxide hydrolase mRNA is increased 3-fold after chronic phenobarbital administration. This level of induction correlates well with the 5-fold induction in catalytic activity of epoxide hydrolase (using styrene 7,8-oxide as substrate) in microsomes isolated from phenobarbital-treated rats. Therefore, we suggest that chronic phenobarbital administration increases the amount of functional epoxide hydrolase in rat liver microsomes by way of an increase in the translatable mRNA level encoding for the enzyme. We do not know whether the increase in mRNA is the result of increased transcription or messenger stability.